The endoplasmic reticulum stress response in disease pathogenesis and pathophysiology

Manalo, Rafael Vincent M.; Medina, Paul Mark B.

doi:10.1016/j.ejmhg.2017.07.004

Cited by 22 publications

(16 citation statements)

References 85 publications

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“…Upon antigen recognition, immune cells undergo proliferation and develop effector functions that result in the influx of proteins into the ER, potentially initiating ER stress. There is a wealth of evidence that indicates that ER stress is a major contributor to disease and inflammation [27,28]. More recently, ER stress, ISR, and UPR have been shown to play a role in T cell development and response.…”

Section: Introductionmentioning

confidence: 99%

Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function

Kemp

Poe

2019

IJMS

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The unfolded protein response (UPR) is a highly conserved pathway that allows cells to respond to stress in the endoplasmic reticulum caused by an accumulation of misfolded and unfolded protein. This is of great importance to secretory cells because, in order for proteins to traffic from the endoplasmic reticulum (ER), they need to be folded appropriately. While a wealth of literature has implicated UPR in immune responses, less attention has been given to the role of UPR in T cell development and function. This review discusses the importance of UPR in T cell development, homeostasis, activation, and effector functions. We also speculate about how UPR may be manipulated in T cells to ameliorate pathologies.

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Section: Introductionmentioning

confidence: 99%

Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function

Kemp

Poe

2019

IJMS

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“…This occurrence is not unusual, since the DAergic neurons that showed an increase in CEP intensity also showed a significant loss in ADE neurons. Hence, an increase in intensity may be indicative of compensation by the neurons remaining, a mechanism similar to a stress response (Manalo and Medina 2018b ). In contrast, there was a non-significant decline in the percentage of intact PDE neurons ( Figure 3(A–F) ), which also correlated to a non-significant change in gentle touch to the tail between treatment groups and the phenotypic control (N2).…”

Section: Resultsmentioning

confidence: 99%

“…An increase in function, therefore, can result in greater expression of proteins and can lead either to neuron growth or merely an increase in GFP expression. In the 60LC10 group, we hypothesise that caffeine at 10 mM is able to promote survival of all neurons despite an additional stressor (60 mM L -DOPA), allowing all neurons to survive but resulting to an increase in GFP proportional to the amount of stress, possibly pointing to the ER stress response (Manalo and Medina 2018b ). A newly discovered mechanism involving mitochondrial dysfunction shows that ROS can increase hop-1 and pink-1 expression in C. elegans, which can lead to motor deficits and neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Manalo

Medina

2020

Pharmaceutical Biology

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Context: L-DOPA is the first-line drug for Parkinson's disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. Objectives: This study determined changes in terms of neurodegeneration, locomotion and mechanosensation in Caenorhabditis elegans (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. Materials and methods: Neurodegeneration was monitored via fluorescence microscopy of GFP-tagged dopaminergic neurons in the head and tail regions of C. elegans. Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60 mM), caffeine (10 mM) or 60 mM L-DOPA þ 10 or 20 mM caffeine (60LC10 and 60LC20) treatments were scored for 3 days (n ¼ 20). Results: L-DOPA (60 mM) reduced CEP and ADE neurons by 4.3% on day 3, with a concomitant decrease in fluorescence by 44.6%. This correlated with reductions in gentle head (À35%) and nose touch (À40%) responses, but improved locomotion (20-75%) compared with vehicle alone. CEP and ADE neuron counts were preserved with caffeine (10 mM) or 60LC10 (98-100%), which correlated with improved mechanosensation (10-23%) and locomotion (18-76%). However, none of the treatments was able to preserve PDE neuron count, reducing the basal slowing response. Discussion and conclusions: Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

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“…Akt, VEGF, MMPs and other important cancer‐phenotype proteins are partners of Hsp90, the latter works as a molecular chaperone and guarantees correct folding of its substrates . Hsp90 inhibition leads not only to targeted destabilization of key oncogenic proteins but also to misfolded protein aggregation, endoplasmic reticulum stress and apoptotic death or autophagy …”

Section: Preclinical Antineoplastic Activity Of Haart Drugsmentioning

confidence: 99%

“…94,198 inhibition leads not only to targeted destabilization of key oncogenic proteins but also to misfolded protein aggregation, endoplasmic reticulum stress and apoptotic death or autophagy. 151,152 Detailed docking analysis has shown that PIs can be potent Hsp90 inhibitors; their binding capacity to Hsp90 decreases in the following order: Nelfinavir, Indinavir, Saquinavir, Ritonavir, Lopinavir, Tipranavir, Darunavir and Amprenavir § . 153 Indeed, among all PIs, nelfinavir seems to have the highest anticancer activity.…”

Section: Preclinical Antineoplastic Activity Of Haart Drugsmentioning

confidence: 99%

HIV‐1, HAART and cancer: A complex relationship

Шмакова

Germini

Vassetzky

2019

Intl Journal of Cancer

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HIV infected people are at higher risk of developing cancer, although it is globally diminished in the era of highly active antiretroviral treatment (HAART). Recently, antioncogenic properties of some HAART drugs were discovered. We discuss the role of HAART in the prevention and improvement of treatment outcomes of cancers in HIV‐infected people. We describe different trends in HAART–cancer relationships: cancer‐predisposing as well as cancer‐preventing. We cover the roles of particular drug regimens in cancer prevention. We also describe the causes of cancer treatment with HAART drugs in HIV‐negative people, including ongoing clinical studies that may directly point to a possible independent anti‐oncogenic activity of HAART drugs. We conclude that despite potent antioncogenic activities of every class of HAART drugs reported in preclinical models, the evidence to date indicates that their independent clinical impact in HIV‐infected people is limited. Improved cancer prevention strategies besides HAART are needed to reduce HIV‐cancer‐related mortality.

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The endoplasmic reticulum stress response in disease pathogenesis and pathophysiology

Cited by 22 publications

References 85 publications

Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function

Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function

Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

HIV‐1, HAART and cancer: A complex relationship

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